NARS1

Protein identityUniProt · HPA

UniProt accession

O43776

Gene

NARS1

Ensembl

ENSG00000134440

Chromosome

18

Canonical length

548 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Asparaginyl-tRNA synthetase is localized to the cytoplasm and belongs to the class II family of tRNA synthetases. The N-terminal domain represents the signature sequence for the eukaryotic asparaginyl-tRNA synthetases. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

548 residues, UniProt reviewed canonical sequence.

>O43776|NARS1
     1  MVLAELYVSD REGSDATGDG TKEKPFKTGL KALMTVGKEP FPTIYVDSQK ENERWNVISK
    61  SQLKNIKKMW HREQMKSESR EKKEAEDSLR REKNLEEAKK ITIKNDPSLP EPKCVKIGAL
   121  EGYRGQRVKV FGWVHRLRRQ GKNLMFLVLR DGTGYLQCVL ADELCQCYNG VLLSTESSVA
   181  VYGMLNLTPK GKQAPGGHEL SCDFWELIGL APAGGADNLI NEESDVDVQL NNRHMMIRGE
   241  NMSKILKARS MVTRCFRDHF FDRGYYEVTP PTLVQTQVEG GATLFKLDYF GEEAFLTQSS
   301  QLYLETCLPA LGDVFCIAQS YRAEQSRTRR HLAEYTHVEA ECPFLTFDDL LNRLEDLVCD
   361  VVDRILKSPA GSIVHELNPN FQPPKRPFKR MNYSDAIVWL KEHDVKKEDG TFYEFGEDIP
   421  EAPERLMTDT INEPILLCRF PVEIKSFYMQ RCPEDSRLTE SVDVLMPNVG EIVGGSMRIF
   481  DSEEILAGYK REGIDPTPYY WYTDQRKYGT CPHGGYGLGL ERFLTWILNR YHIRDVCLYP
   541  RFVQRCTP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NARS1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

126 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NARS1.

Disease | AllUniProt

Conditions NARS1 is implicated in, by any mechanism.

• Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG) MIM:619091
• Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG) MIM:619092

Disease | GeneticClinVar

23 pathogenic / likely-pathogenic of 236 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities
• Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities
• Mitochondrial complex 1 deficiency, nuclear type 35
• Neurodevelopmental disorder
• Developmental disorder

ReferencesPubMed · IEDB

Publications for NARS1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.78

gnomAD pLI

0

DepMap mean gene effect

-1.85

DepMap dependency class

pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• asparaginyl-tRNA aminoacylation
• cell migration
• cerebral cortex development
• tRNA aminoacylation for protein translation

Molecular functions

• asparagine-tRNA ligase activity
• ATP binding
• CCR3 chemokine receptor binding
• nucleic acid binding
• protein dimerization activity

Cellular components

• cytoplasm
• cytosol
• extracellular exosome

Protein domainsUniProt · Pfam · InterPro

• Aspartyl/Asparaginyl-tRNA synthetase, class IIb
• Aminoacyl-tRNA synthetase, class II (D/K/N)
• OB-fold nucleic acid binding domain, AA-tRNA synthetase-type
• Asparagine-tRNA ligase
• Aminoacyl-tRNA synthetase, class II
• Nucleic acid-binding, OB-fold
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• tRNA synthetases class II (D, K and N)
• OB-fold nucleic acid binding domain
• Asparagine--tRNA ligase, N-terminal domain
• Asparaginal-tRNA synthetase, N-terminal domain

KeywordsUniProt

• Acetylation
• Aminoacyl-tRNA synthetase
• ATP-binding
• Cytoplasm
• Epilepsy
• Intellectual disability
• Ligase
• Neurodegeneration
• Nucleotide-binding
• Phosphoprotein
• Protein biosynthesis